| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 School of Pharmacy, University of Wyoming, 1000 E. University Avenue, Laramie, 82071, United States
2 Animal Science, University of Wyoming, 1000 E University Avenue, Dept 3684, Laramie, 82071, United States
3 Cardiovascular Research Institute, New York Medical College, Valhalla, New York, 10595, United States
4 Dept. of Medicine, New York Medical College, Vosburgh Pavillion, Room 303, Valhalla, New York, 10595-1190, United States
5 University of Wyoming, United States
* To whom correspondence should be addressed. E-mail: jren{at}uwyo.edu.
Aging is associated with hepatic growth hormone resistance resulting in a fall in serum insulin-like growth factor-1 (IGF-1) level. However, whether loss of IGF-1 contributes to cardiac aging is unclear. This study was designed to examine the effect of cardiac overexpression of IGF-1 on cardiomyocyte contractile function in young (3 mo) and old (26-28 mo) mice. Cardiomyocyte contractile function was evaluated including peak shortening (PS), time-to-90% PS, time-to-90% relengthening (TR90) and maximal velocity of shortening/relengthening (± dL/dt). Levels of advanced glycation endproduct (AGE), protein carbonyl, sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban (PLB) and Na+-Ca2+ exchanger (NCX) were assessed by Western blot. SERCA activity was measured by 45Ca2+ uptake. Aging induced a decline in plasma IGF-1 levels. Aged cells exhibited depressed ± dL/dt, prolonged TR90 and a steeper PS decline in response to increasing stimulus frequency compared with young myocytes. IGF-1 transgene alleviated aging-induced loss in plasma IGF-1 and aging-induced mechanical defects with little effect in young mice. The beneficial effect of IGF-1 transgene on aging-associated cardiomyocyte contractile dysfunction was somewhat mimicked by short-term in vitro treatment of recombinant IGF-1 (500 nM). AGE and protein carbonyl levels were higher in aged mice which were not affected by IGF-1. Expression of SERCA2a (but not NCX and PLB) and SERCA activity were reduced with aging, which was ablated by the IGF-1 transgene. Collectively, our data suggest beneficial role of IGF-1 in aging-induced cardiac contractile dysfunction, possibly related to improved Ca2+ uptake.
This article has been cited by other articles:
|
|
 |
|
  A. Csiszar, N. Labinskyy, V. Perez, F. A. Recchia, A. Podlutsky, P. Mukhopadhyay, G. Losonczy, P. Pacher, S. N. Austad, A. Bartke, et al. Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H1882 - H1894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Groban, H. Jobe, M. Lin, T. Houle, D. A. Kitzman, and W. Sonntag Effects of Short-Term Treadmill Exercise Training or Growth Hormone Supplementation on Diastolic Function and Exercise Tolerance in Old Rats J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2008; 63(9): 911 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-J. Kim, M. Abdellatif, S. Koul, and G. J. Crystal Chronic treatment with insulin-like growth factor I enhances myocyte contraction by upregulation of Akt-SERCA2a signaling pathway Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H130 - H135. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
